Although electronic pacemakers are currently the mainstay of therapy for heart block and other electrophysiological abnormalities, they are not optimal. Among their shortcomings are limited battery life, the need for permanent catheter implantation into the heart, and lack of response to autonomic neurohumors. (1) For these reasons, several gene therapy approaches have been explored as potential alternatives. These include either overexpression of β2-adrenergic receptors (2, 3) use of a dominant-negative construct to suppress inward rectifier current when expressed together with the wild-type gene Kir2.1 (4) and implantation of vectors carrying the pacemaker gene, HCN2, into atrium (5) or bundle branch system. (6) A problem inherent in some of these approaches (2-6) is the use of viruses to deliver the necessary genes. Although the vectors have been replication-deficient adenoviruses that have little infectious potential, these incorporate the possibility of only a transient improvement in pacemaker function as well as potential inflammatory responses. The use of retroviruses and other vectors, although not attempted as yet for biological pacemakers, carries a risk of carcinogenicity and infectivity that is unjustified, given the current success of electronic pacemakers. Attempts to use embryonic human stem cells to create pacemakers are still in their infancy and carry the problems of identifying appropriate cell lineages, the possibility of differentiation into lines other than pacemaker cells, and potential for neoplasia (see overview (7)).